Caveolin-1 function at the plasma membrane and in intracellular compartments in cancer

Abstract

Caveolin-1 (CAV1) is commonly considered to function as a cell surface protein, for instance in the genesis of caveolae. Nonetheless, it is also present in many intracellular organelles and compartments. The contributions of these intracellular pools to CAV1 function are generally less well understood, and this is also the case in the context of cancer. This review will summarize literature available on the role of CAV1 in cancer, highlighting particularly our understanding of the canonical (CAV1 in the plasma membrane) and non-canonical pathways (CAV1 in organelles and exosomes) linked to the dual role of the protein as a tumor suppressor and promoter of metastasis. With this in mind, we will focus on recently emerging concepts linking CAV1 function to the regulation of intracellular organelle communication within the same cell where CAV1 is expressed. However, we now know that CAV1 can be released from cells in exosomes and generate systemic effects. Thus, we will also elaborate on how CAV1 participates in intracellular communication between organelles as well as signaling between cells (non-canonical pathways) in cancer.

Keywords: Caveolin-1; Localization; Metastasis; Organelles.

Fig. 1

Subcellular localizations of CAV1. Representative scheme that summarizes the subcellular compartments where CAV1 is suggested to be localized as supported by the UniProt, PSORT II, MGI, and LocDB databases and select references (see Table 1). According to the data, CAV1 is present in the plasma membrane, Golgi apparatus, ER, nucleus, endocytic as well as exocytic vesicles, multivesicular bodies (MVB), and lipid droplets. Additional evidence places CAV1 at mitochondria-ER interphase sites (localizing CAV1 indirectly to mitochondria), referred to as mitochondria-associated ER membranes (MAMs), as well as lysosomal, peroxisomal, and exosomal membranes, as will be discussed in this review

Fig. 2

Signaling events modulated by CAV1 at the plasma membrane (canonical role) and at several subcellular localizations (non-canonical role). Proteins regulated by CAV1 functioning as a tumor suppressor are indicated in purple. Alternatively, those proteins modulated by CAV1 functioning as a tumor promoter are shown in green. CSD, caveolin-1 scaffolding domain; pY14-CAV1, phosphorylated caveolin-1; MVB, multivesicular body; MAMs, mitochondria-associated membranes. For protein abbreviations and more details, see the respective sections of the main text